CN102240294A - Medicament composition, and preparation and application thereof - Google Patents
Medicament composition, and preparation and application thereof Download PDFInfo
- Publication number
- CN102240294A CN102240294A CN 201010169348 CN201010169348A CN102240294A CN 102240294 A CN102240294 A CN 102240294A CN 201010169348 CN201010169348 CN 201010169348 CN 201010169348 A CN201010169348 A CN 201010169348A CN 102240294 A CN102240294 A CN 102240294A
- Authority
- CN
- China
- Prior art keywords
- aspirin
- diosgenin
- pharmaceutical composition
- preparation
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a medicament composition of aspirin and diosgenin in view of the limitations of antithrombotic medicaments. The composition has antithrombotic activity significantly higher than aspirin, can significantly reduce the therapeutic dose of aspirin, simultaneously has gastric mucosal protective effect, and can be safely used for long term.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of pharmaceutical composition, its preparation with anti-thrombosis function, and the application in cardiovascular and cerebrovascular disease prevention, treatment.
Technical background
Platelet aggregation and thrombosis are the major reasons of ischemic heart and brain damage.Platelet activation, stick and gathering is one of thrombotic initiating agent of intra-arterial, in morbidities such as atherosclerosis and coronary events (unstable angina pectoris, acute myocardial infarction, heart ischemia sudden death), apoplexy, play key effect.Therefore, antiplatelet and anticoagulant therapy have become the focus that reduces clinical ischemic incident treatment.
Aspirin is the choice drug of control artery thrombosis, and the thrombosis that is used to prevent transient cerebral ischemic attack, myocardial infarction, atrial fibrillation, arteriovenous fistula or other postoperatives also is used for unstable angina pectoris.Aspirin optionally suppresses COX-I, thromboxane A in the irreversible minimizing platelet
2(TXA
2) generation, thereby anticoagulant suppresses thrombosis.Through comprising the clinical trial of tens thousand of routine patient's placebo groups, the proof aspirin has reduced the danger of arterial thrombus, reduce cardiovascular event and death risk that atherosclerosis comprises MI, stability, unstable angina pectoris, apoplexy, TIA and peripheral vascular disease patient, its relative risk reduces 35-39%.Aspirin 75～1200mg/d reduces myocardial infarction and death risk 50%.Low-dosage aspirin is the key product of prevention cardiovascular and cerebrovascular vessel incident such as heart disease outbreak and apoplexy, yet, even under low dose, also peptic ulcer and gastrointestinal symptom can occur.(MKt L, 2009,36 (19)) may develop into the GI symptom up to 1/3 patient who takes low-dosage aspirin according to statistics.If the danger of 3 times high great CV incident then in 1～2 week of drug withdrawal, can occur because of the inactive aspirin of GI problem.And have statistics to show in taking the tremulous pulse medicated porridge sample disease patient of various dose aspirin, 20～30% drug resistance that can produce aspirin are arranged.Though wide spectrum medicament for resisting platelet aggregation clopidogrel activity is better than aspirin but still has the gastrointestinal hemorrhage risk in the clinical use, and this toxic and side effects risk and aspirin comparison no significant difference.In a word, gastrointestinal side effect and the chemical sproof increase in taking for a long time is present anti-thrombosis drug problem demanding prompt solution.
The aspirin anti-thrombosis function is not relevant with dosage, and gastrointestinal ulceration, hemorrhage risk have substantial connection with dosage.Drug effect by drug combination raising aspirin reduces using dosage, and prevents that by the other drug of uniting use gastrointestinal side effect from should be a useful approach.
Diosgenin (Diosgenin) is the natural steroid compounds that is distributed widely in the plant, for a long time, receives publicity mainly as the synthetic initiation material of steroid hormone class medicine.Be that the saponin component of parent nucleus has cardiovascular pharmacological activity in various degree with the diosgenin, wherein representational product has DIAOXINXUE KANG.Bibliographical information (Ma Haiying etc., the Chinese Hospitals pharmaceutical journal, 2002,22 (6), 323-325) diosgenin is the active substance that natural saponin component oral administration is absorbed into blood, it has the platelet aggregation inhibitory activity stronger than natural saponin.We discover that diosgenin is individually dosed, with the aspirin Isodose under show very weak anti-thrombosis activity, and be used in combination the anti-thrombosis activity (seeing the embodiment of the invention 1) that can significantly improve aspirin with aspirin.
It is clinical that the natural steroid saponins medicine that contains the diosgenin parent nucleus is used for the cardiovascular diseases for a long time, and its safety gets the nod, and bibliographical information (Wang Xiaopeng is arranged; foreign medical science Chinese medicine fascicle; 2004,26 (3), 138-141) diosgenin has gastric mucosal protective effect.Therefore, the compositions of diosgenin and existing anti-thrombosis drug aspirin composition probably becomes a kind of safe and effective anti-thrombosis drug.
Summary of the invention
The present invention provides a kind of pharmaceutical composition in view of the limitation of existing anti-thrombosis drug.The said composition anti-thrombosis activity is significantly higher than simple use aspirin, can significantly reduce the therapeutic dose of aspirin, has gastric mucosal protective effect simultaneously, but long-term safety is used.
Pharmaceutical composition with anti-thrombosis activity provided by the invention is made up of aspirin and diosgenin.The said composition proportion of composing is an aspirin: diosgenin weight ratio 1: 1-1: 20 (W: W) preferred 1: 1-1: 10, more preferably 1: 1-1: 5.
Another object of the present invention provides the preparation that contains this pharmaceutical composition and pharmaceutically acceptable adjuvant.
Provided by the inventionly contain the preparation that pharmaceutical composition of the present invention and pharmaceutics can be accepted adjuvant, be preferably selected from oral formulations, described oral formulations includes but not limited to solid orally ingestible and liquid oral medicine.
Oral formulations of the present invention is solid orally ingestible more preferably, and described solid orally ingestible is preferably selected from conventional tablet, granule, capsule, sustained-release preparation, powder, drop pill, solid dispersion, effervescent tablet, enteric coated tablet, enteric coated capsule.Described sustained-release preparation is preferably selected from slow-release tablet agent, capsule or granule.
Of the present inventionly contain the preparation that pharmaceutical composition of the present invention and pharmaceutics can be accepted adjuvant, wherein the pharmaceutics pharmaceutic adjuvant acceptable comprises diluent, lubricant, binding agent, disintegrating agent, stabilizing agent etc.
Diluent of the present invention includes but not limited to starch, microcrystalline Cellulose, sucrose, dextrin, lactose, Icing Sugar, glucose, low molecular dextran, Kaolin, sodium chloride, mannitol etc.; Described lubricant includes but not limited to magnesium stearate, stearic acid, boric acid, sodium chloride, enuatrol, DL-leucine, sodium laurylsulfate, Macrogol 4000-6000, the husky mother in pool Lip river etc.; Described binding agent includes but not limited to water, ethanol, starch slurry, syrup, gelatin, methylcellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, sodium alginate, ghatti gum, polyvinylpyrrolidone etc.; Described disintegrating agent includes but not limited to starch, carboxymethyl starch sodium, citric acid, tartaric acid, low-substituted hydroxypropyl cellulose etc.; Described stabilizing agent comprises but is not limited to polysaccharide such as acacin, agar, alginic acid, guar gum, tragacanth, acryllic acid resin, cellulose ether and carboxymethyl carapace ester etc.
Pharmaceutical composition provided by the invention forms at the animal antithrombotic and shows in the test than aspirin and the better anti-thrombosis activity of the independent use of diosgenin, can significantly reduce the aspirin using dosage and can effectively lower gastrointestinal side effect because of diosgenin itself has gastric mucosal protective effect.Therefore, this pharmaceutical composition can be used for the prevention and the treatment of cardiovascular and cerebrovascular disease for a long time.
Embodiment
The present invention is described further below in conjunction with embodiment.Embodiment only is indicative, and never meaning limits the scope of the invention by any way.
Embodiment 1
Aspirin-diosgenin compositions anti-thrombosis function
1. material:
1.1 reagent:
Heparin sodium: lot number is sold in chemical reagent wholesale department, Tianjin: 891125.
Sodium chloride: Tianjin City Tanggu chemical reagent factory product.
Sodium carboxymethyl cellulose: Tianjin good fortune chemical reagent in morning factory product, lot number: 20050407.
Tween 80: Tianjin fine chemicals company limited product, lot number: 920311.
1.2 medicine
Aspirin-diosgenin compositions; Tianjin Inst. of Materia Medica original new drug research center provides;
Aspirin: keep sample in organizing;
Diosgenin: Tianjin Inst. of Materia Medica original new drug research center provides;
Compound method is 180mg+10d tween+1%CMC-Na to 18ml;
1.3 animal
The Wistar rat, male, body weight 260-320g is available from Institute of Radiation Medicine, Chinese Academy of Medical Sciences.
1.4 instrument
BS124S type electronic balance: Beijing Sai Duolisi instrument system company limited product.
HZS-D water-bath oscillator: east, Harbin connection electronic technology development corporation, Ltd. product.
2. method:
Rat is divided into 7 groups by weight average, is respectively model group, positive drug aspirin group is subjected to five groups of reagent TY-606.Oral administration 100mg/kg, successive administration 3 times, 1 hour anesthetized animal (ip) fix for pentobarbital sodium, 54mg/kg, separates right common carotid artery and left external jugular vein by dorsal position after the last administration.Put into the silk thread of a long 6cm in the stage casing of polyfluortetraethylene pipe.(50u/ml) is full of polyfluortetraethylene pipe with heparin-saline solution.After an end of polyfluortetraethylene pipe inserts left external jugular vein, inject the anticoagulant heparin of 50u/kg exactly by polyfluortetraethylene pipe, and then the other end of polyfluortetraethylene pipe is inserted right common carotid artery.Open bulldog clamp, blood flow in the polyfluortetraethylene pipe from right common carotid artery, returns left external jugular vein.Herba Clinopodii in behind the open blood flow 15min takes out silk thread rapidly and weighs, and gross weight deducts silk thread weight and promptly gets wet weight of thrombus.
Table 1. aspirin-diosgenin compositions antiplatelet forms activity
| Group | Dosage (mg/kg) | Number of animals (only) | Bolt heavy (mg) |
| Model | --- | 8 | 26.9±9.3 |
| Aspirin | 100 | 10 | 14.5±8.2** |
| Diosgenin | 100 | 10 | 21.6±7.8* |
| Aspirin: diosgenin (1: 2.5) | 100 | 10 | 10.9±7.3** |
| Aspirin: diosgenin (1: 5) | 100 | 10 | 13.7±12.3** |
| Aspirin: diosgenin (1: 10) | 100 | 10 | 11.3±8.4** |
* and model group compare, P＜0.01, * P＜0.05
Embodiment 2
Aspirin 50g, diosgenin 50g granulate with an amount of tartrated 15% starch slurry, and drying adds 10% dried starch, 5% Pulvis Talci tabletting, get 1000, specification: 100mg/ sheet
Embodiment 3
Aspirin 40g, diosgenin 60g, lactose-microcrystalline cellulose (5: 1) 100g get the granulation of 15% starch slurry with containing tartaric acid in right amount, and drying adds 10% dried starch, 5% Pulvis Talci tabletting, gets 1000, specification: 200mg/ sheet
Embodiment 4
Aspirin 30g, diosgenin 70g granulate with an amount of tartrated 15% starch slurry, and drying adds 10% dried starch, 5% Pulvis Talci tabletting, gets 1000, specification: 100mg/ sheet
Embodiment 5
Aspirin 20g, diosgenin 80g get the granulation of 15% starch slurry with containing tartaric acid in right amount, and drying adds 10% dried starch, 5% Pulvis Talci tabletting, gets 1000, specification: 100mg/ sheet
Embodiment 6
Aspirin 10g, diosgenin 90g, lactose-microcrystalline cellulose (5: 1) 100g granulate with an amount of tartrated 15% starch slurry, add 10% dried starch, 5% Pulvis Talci tabletting, get 1000, specification: 200mg/ sheet
Embodiment 7
Aspirin-diosgenin (1: 5) 100g granulates with an amount of tartrated 15% starch slurry, and drying is sieved, and is encapsulated, gets 1000, specification: 100mg/ grain
Embodiment 8
Aspirin-diosgenin (1: 10) 100g, lactose 100g granulates with the starch slurry that contains citric acid in right amount, and drying is sieved, and is encapsulated, gets 1000, specification: 200mg/ grain
Embodiment 9
Aspirin-diosgenin (1: 2.5) 100g gets the granulation of 15% starch slurry with containing tartaric acid in right amount, and drying is sieved, and adds 10% starch, 5% Pulvis Talci tabletting, gets 1000, with acrylic resin II solution coating, gets enteric coated tablet.
Embodiment 10
Aspirin-diosgenin (1: 20) 100g, dextrin 50g, lactose 50g granulates with the starch slurry that contains citric acid in right amount, and drying is sieved, and is encapsulated, gets 1000, specification: 200mg/ grain
Claims (9)
1. a pharmaceutical composition is characterized in that being made up of aspirin and diosgenin.
2. the described pharmaceutical composition of claim 1, the composition weight ratio that it is characterized in that aspirin and diosgenin is 1: 1-1: 20.
3. the described pharmaceutical composition of claim 2, the composition weight ratio that it is characterized in that aspirin and diosgenin is 1: 1-1: 10.
4. the described pharmaceutical composition of claim 3, the composition weight ratio that it is characterized in that aspirin and diosgenin is 1: 1-1: 5.
5. the described pharmaceutical composition of claim 4, the composition weight ratio that it is characterized in that aspirin and diosgenin is 1: 1-1: 3.
6. pharmaceutical preparation contains pharmaceutical composition and appropriate carriers or the excipient of claim 1-4.
7. the described pharmaceutical preparation of claim 5 comprises solid orally ingestible, liquid oral medicine, injection.
8. the described pharmaceutical preparation of claim 6 is preferably solid orally ingestible.
9. the application of the described pharmaceutical composition of claim 1-4 in the preparation anti-thrombosis drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010169348A CN102240294B (en) | 2010-05-12 | 2010-05-12 | Medicament composition, and preparation and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010169348A CN102240294B (en) | 2010-05-12 | 2010-05-12 | Medicament composition, and preparation and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102240294A true CN102240294A (en) | 2011-11-16 |
| CN102240294B CN102240294B (en) | 2012-10-17 |
Family
ID=44958658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010169348A Active CN102240294B (en) | 2010-05-12 | 2010-05-12 | Medicament composition, and preparation and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102240294B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104173360A (en) * | 2013-05-27 | 2014-12-03 | 天津药物研究院 | Antithrombotic pharmaceutical composition, and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1640407A (en) * | 2004-01-06 | 2005-07-20 | 李细海 | Anti-thrombus small-dose aspirin injection agent and its preparing method |
-
2010
- 2010-05-12 CN CN201010169348A patent/CN102240294B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1640407A (en) * | 2004-01-06 | 2005-07-20 | 李细海 | Anti-thrombus small-dose aspirin injection agent and its preparing method |
Non-Patent Citations (1)
| Title |
|---|
| 《中国医院药学杂志》 20021231 马海英等 黄山药总皂苷和薯蓣皂苷元抗高脂血症及体外抗血小板聚集的比较 323-325 1-9 第22卷, 第6期 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104173360A (en) * | 2013-05-27 | 2014-12-03 | 天津药物研究院 | Antithrombotic pharmaceutical composition, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102240294B (en) | 2012-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102024699B1 (en) | Complex formulation comprising clopidogrel and asprin | |
| JP2011512406A (en) | Compound preparation | |
| KR20130048335A (en) | Combination of clopidogrel and aspirin | |
| CN1682719B (en) | Enteric soluble coating slow releasing tablet containing huperzine A and preparing method | |
| US20160120869A1 (en) | Solid pharmaceutical dosage form | |
| CN103479583B (en) | Potassium sodium dehydroandroan drographolide succinate enteric dry suspension and preparation method thereof | |
| CN104876903A (en) | Crystallization form of dihydromyricetin, preparation method thereof and pharmaceutical composition containing the same | |
| CN103520129A (en) | Montelukast sodium pulse release preparation | |
| CN102240294B (en) | Medicament composition, and preparation and application thereof | |
| CN104138376A (en) | A sustained release agent improving anoxia endurance | |
| CN109875971A (en) | A kind of Berberine hydrochloride sustained release tablets and preparation method thereof | |
| CN101690724A (en) | Piperazine ferulate enteric preparation and preparation method thereof | |
| CN112569190B (en) | Oral administration preparation of pulsatilla chinensis saponin B4 and preparation method thereof | |
| CN103800336A (en) | Composition with anti-thrombus active medicine | |
| CN102038642A (en) | Ginkgolide B solid dispersoid and preparation method thereof | |
| CN101269056B (en) | Metoprolol salt oral administration impulse pellet preparation | |
| CN102657615A (en) | Vincamine sustained-release pellet preparation and preparation method thereof | |
| CN101773485A (en) | Sustained-release preparation using S-metoprolol and dihydropyridine calcium channel blocker as active components and preparation method and use thereof | |
| CN102755319B (en) | Pharmaceutical composition containing prasugrel and carvedilol, and purpose thereof | |
| CN101327215B (en) | Medicament composition containing protoberberine type alkaloids | |
| CN115569125B (en) | Sinomenine hydrochloride oral delayed release pulse micropill, its preparation and preparation method | |
| WO2017219453A1 (en) | Valsartan dispersible tablet and preparation method thereof | |
| CN100522179C (en) | Medicine composition for treating cardiovascular and cerebrovascular disease and its preparation method | |
| CN113209037B (en) | Oxiracetam osmotic pump controlled release tablet and application thereof | |
| CN100434087C (en) | Compound oral prepn of muskone and total arasaponin and its application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address |
Address after: 300301 No. 306, Huiren Road, Binhai Science Park, Binhai high tech Zone, Binhai New Area, Tianjin Patentee after: Tianjin Institute of Pharmaceutical Research Co.,Ltd. Address before: 300193 Tianjin City, Nankai District Anshan West Road No. 308 Patentee before: Tianjin Institute of Pharmaceutical Research |
|
| CP03 | Change of name, title or address | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220330 Address after: 300301 No. 29, Huixin Road, Binhai Science Park, Binhai high tech Zone, Tianjin Binhai New Area, Tianjin Patentee after: TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH PHARMACEUTICAL RESPONSIBLE CO.,LTD. Address before: 300301 No. 306, Huiren Road, Binhai Science Park, Binhai high tech Zone, Binhai New Area, Tianjin Patentee before: Tianjin Institute of Pharmaceutical Research Co.,Ltd. |
|
| TR01 | Transfer of patent right |